Successful adaptation to chronic stress is a dynamic process that is dependent on the attributes of the stress exposure, such as severity, modality and duration. Stress “habituation” is thought to be an important adaptive response to repeated challenge, wherein responses to a given stressor decrease upon repeated exposure and thus reduce the overall physiological burden (e.g., cumulative effects of glucocorticoid secretion) with time. Animals can generally habituate to repeated stressors (Grissom and Bhatnagar, 2009). This is evident by a marked reduction in HPA axis activation with repeated exposure to the same stimulus (Figure 3). Habituation is observed after exposure to a wide array of stimuli, ranging from mild (e.g., novel environment) to severe (limb and head immobilization) (Campmany et al., 1996; Grissom and Bhatnagar, 2009). The rate of habituation is dependent on the severity of the stressor (Garcia et al., 2000). Habituation is likely mediated by diminution of central responses to the stressor; for example, activation of c-fos expression in the medial parvocellular PVN is markedly reduced in the PVN following repeated restraint stress (Girotti et al., 2006). Habituation limits
